We investigated the mechanism of luteal regression using rat corpus luteum and human luteinized granulosa cells. We got three different findings these 2 years.First, Tissue inhibitor of metalloproteinase (TIMP) mRNA expression was reduced by prolactin (PRL) in structural luteolysis of the rat. As we reported before, matrix metallopreoteinase (MMP)-2 was significantly increased in PRL-incuced structural luteolysis. Actural MMP-2 activity is well known to be regulated by TIMP expression in vivo. Reduced TIMP-1 mRNA expression is thought to elevate MMP-2 activity in vivo. These results revealed that degradation of extracellular matrix is associated with the mechanism of structural luteolysis in the rat. Apoptosis was occured in PRL-induced structural luteolysis in the rat. We also showed apoptosis did not occured in functional luteolysis. Thease results showed that the loss of weight in structural involution of rat corpus luteum is related to apoptosis (programed cell death).Second, perox
… Moreide reduced ATP levels of human luteinized granulosa cells. As we reported, H_2O_2 treatment reduced cAMP and progesterone production in human luteinized granulosa cells. We investigated that depletion of ATP may be related to the inhibition of cAMP synthesis. While 3-aminobenzamide, which is an inhibitor of poly (ADP-ribose) polymerase, blocked peroxide-induced ATP depletion, peroxide reduced hCG-stimulated cAMP production. Thease results indicated that ATP depletion is not associated with peroxide-reduced cAMP synthesis.Third, prostaglandin F_2_<alpha> (PGF) activated phospholipase (PL) D in rat luteal cells.We raported before that PGF activated PLA_2 and PLC in rat luteal cells. PCL activation is not reported to be associated with PGF-induced luteolysis. We examined if PLD activation may be the second signal of PGF-induced luteolysis using oleic acid-labeled rat luteal cells under the presence of ethanol.The result showed that PLD activation may be second messenger in PGF-treated rat luteal cells. Less